Recent investigations have demonstrated the presence of two types of hair cells in the otolithic endorgans of a fish. One of these hair cell types ultrastructurally resembles the mammalian vestibular type II hair cell. The other cell type closely resembles the mammalian type I hair cell. Similar to mammalian type I hair cells, those in fish are damaged by the ototoxic drug gentamicin sulphate. Studies have now shown that sensory hair cells in canal neuromasts of the lateral line are damaged by gentamicin while hair cells in superficial lateral line neuromasts are not. These results suggest that the lateral line may have two types of hair cells. This proposal uses ultrastructural and neuroanatomical methods to test the hypothesis that different lateral line neuromasts have different types of hair cells. If two types of hair cells are present, this will provide an excellent system for future studies of function of hair cells of different types. In particular, since the lateral line lies at the surface of the fish, the hair cells are readily accessible and amenable to experimental study. In addition, the proposed work will examine the response of lateral line hair cells to aminoglycoside antibiotics with the intent of developing a model system for future work with such drugs. The lateral line has the advantage of providing an in vivo experimental system that, unlike the ear, is easily accessible for analysis. It may be possible to develop a system whereby a single animal can be used for a time-series analysis of the effects of ototoxic drugs by sequentially sampling different regions of the lateral line during the course of an experiment. In the studies of the effect of ototoxic drugs on the lateral line, questions to be asked include: (a) the extent of damage to sensory hair cells of the lateral line by ototoxic drugs and whether the damage parallels that occurring in the ear; (b) the time course of changes in the hair cells during drug treatment; (c) whether different regions of the lateral line in a single animal can be used for sequential studies; and (d) whether hair cells of the lateral line regenerate after drug treatment.